Evaluate the safety and efficacy of personalized network-guided transcranial magnetic stimulation for treating behavioral and psychological symptoms in patients with Alzheimer's disease.
All participants will undergo a series of medical evaluations before and after repetitive transcranial magnetic stimulation (rTMS), including physical examination and routine laboratory tests. After meeting the eligibility criteria and providing written informed consent, each participant will complete cognitive assessments and receive rTMS treatment at the First Affiliated Hospital of Anhui Medical University. Eligible participants will be randomly assigned to the real rTMS group or the sham rTMS group using a random-number table. The individualized stimulation target for each participant will be determined based on the participant's own magnetic resonance imaging data and a predefined BPSD network. Participants will then receive either real or sham rTMS treatment for two weeks. Sham stimulation will be delivered using a sham coil. Except for the stimulation coil, all experimental procedures will be identical between the two groups. Based on a statistical power of 0.80, an effect size of 0.98, a two-sided significance level of 0.05, and an anticipated dropout rate of 10%, the final sample size will be 20 participants per group. This is a double-blind study in which both participants and clinical raters will be blinded to group allocation. Only one researcher responsible for randomization will have access to the allocation list. Each participant will receive rTMS treatment for 14 days. Before treatment, a trained researcher will administer cognitive assessments and neuropsychological tests. The primary outcome will be the total score of the Neuropsychiatric Inventory (NPI). Secondary assessments will include measures of cognitive function, including the ADAS-Cog, MoCA, MMSE, DST, Stroop test, BNT-30, VFT, and CDT; memory function assessed by the CAVLT; emotional symptoms assessed by the HAMA and HAMD; and treatment tolerability. All assessments will be completed within two days. Participants will also undergo multimodal MRI and electroencephalography (EEG) examinations. After the final rTMS session, treatment-related adverse events will be assessed, and participants will be instructed to answer relevant questions based on their condition during the previous 14 days. Participants will also complete the same neuropsychological assessment battery as at baseline and undergo multimodal MRI and EEG examinations again.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
40
Neuronavigated Theta-Burst Transcranial Magnetic Stimulation Other Name:
Neuronavigated Theta-Burst Transcranial Magnetic Stimulation Other Name:
Anhui Medical University
Hefei, Anhui, China
Neuropsychiatric Inventory (NPI)
The Neuropsychology Scale (NPI) evaluates 12 neuropsychiatric disorders which included 10 neuropsychiatric symptoms and 2 autonomic neurological symptoms based on the caregiver's perception of the patient's behavior and the perceived distress. Each item was evaluated for its occurrence frequency (1-4 points) and severity (1-3 points). The frequency and severity were multiplied to obtain the score (0-12 points) of each item.The patient's assessment rating ranges from 0 to 144, and the caregiver's distress rating score is 0 to 60. The lower the score, the lighter the symptoms.
Time frame: Baseline and 2 weeks
Alzheimers Disease Assessment Scale Cognitive section (ADAS-Cog)
The changes in Alzheimers Disease Assessment Scale Cognitive section (ADAS-Cog) will constitute the major research outcome measure used to assess response to transcranial magnetic stimulation (TMS). The ADAS-COG scale tests orientation, language, structure, use of ideas, immediate recall of words and word re-recognition, and consists of 11 questions out of a possible 70 points, with the higher the score the more cognitively impaired.
Time frame: Baseline and 2 weeks
Mini Mental State Examination (MMSE)
The changes in MMSE will constitute the primary research outcome. The full name of MMSE is mini-mental state examination, and the scale consists of 30 subject, include the following seven aspects: time orientation, place orientation, immediate memory, attention and calculation, delay memory, language, visual space. One point is awarded for each question correctly answered during MMSE evaluation. If subject give the wrong answer or don't know answer he/she awarded 0 score, scope of scale score of 0 to 30 points. The higher the score, the better. In this study, changes in MMSE scores before and after treatment were used as secondary outcome measure.
Time frame: Baseline and 2 weeks
Montreal Cognitive Assessment (MoCA)
The changes in MoCA will be used to assess the response to TMS. MoCA was developed by Nasreddine et al. based on clinical experience and reference to the MMSE cognitive items and scores, and the final version was finalized in November 2004. The investigators adopted a localized version (Mandarin version#includes 2 alternative versions) in line with the Chinese cultural background. It includes 11 inspection items in 8 cognitive fields, including visual structure skills, executive function, naming, attention and calculation, language, abstract thinking, memory, and orientation. The normal score range from 26 to 30. Anyone who has been education for less than 12 years will need to add one point to his final score. The final score of the higher the better.
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Time frame: Baseline and 2 weeks
Digital Span Test; Forward and Backward (DST)
The changes in DST will constitute the secondary research outcome. Digital span test (DST) was commonly used to evaluate attention ability and instantaneous memory ability. There are two types of test: forward (0-14) and backward (0-13). In the forward test, the subjects were asked to retell the the digits immediately after hearing it untilthey could not be repeated correctly. In backward test, the subjects were asked to repeat a set of numbers in reverse order until they could not be repeated correctly. The length of the last set of Numbers correctly repeated by the subjects was the final score, forward and backward are counted separately. The higher the score, the better.
Time frame: Baseline and 2 weeks
Hamilton Depression Scale (HAMD)
Hamilton Depression Scale (HAMD) compiled by Hamilton in 1960, is the most common clinical to assess Depression Scale. In this study, we selected the HAMD version with 17 questions. Subjects were assessed for their depression in the past week. Each question scored between 0 and 4 points. Higher scores indicate more depressive symptoms. The severity of the disease and the therapeutic effect can be evaluated after treatment.
Time frame: Baseline and 2 weeks
Hamilton Anxiety Scale (HAMA)
Hamilton Anxiety Scale (HAMA) was compiled by Hamilton in 1959. It was one of the most commonly used scales in psychiatric clinic, including 14 items. It is often used in clinical diagnosis and degree classification of anxiety disorder. The subjects were assessed for their anxiety in the past week. Each question scored between 0 and 4 points. The higher the score, the more symptoms of anxiety.
Time frame: Baseline and 2 weeks
The Stroop color word test
The Stroop color word test was developed by Stroop in 1935 and is used to evaluate the attention function of the subject. The subject is required to correctly read the target color on the stimulus card and record the completion time. The final completion time is the score of the participant. The shorter the time used, the better the performance of the subjects.
Time frame: Baseline and 2 weeks
TMT (Trail Making Test)
The Trail Making Test (TMT) is divided into two parts, part A and part B. Part A requires the subject to connect 25 Numbers on the paper in sequence, and part B requires the subject to connect 25 Numbers of different colors alternately in sequence. The time it takes for the subject to complete all the Numbers is the subject's final score.
Time frame: Baseline and 2 weeks